Role of SIRT1 in epigenetics

Abstract

Epigenetic markers are of great significance in biological systems closely related to genome stability, gene transcription, metabolic regulation, and human diseases. Sirtuins are specially named NAD+-dependent class III histone deacetylases that can catalyze the deacylation of modified lysines, which exist as a major group of posttranslational modifications (PTMs) on both nucleic and cytoplasmic proteins. Among the seven sirtuin enzymes 1-7, sirtuin 1 (SIRT1) can catalyze the deacetylation reaction on both histones and many important nonhistone proteins, serving as a key conjunction between epigenetics, metabolism, and human health. In this chapter, we will begin with the basic introduction of SIRT1 biochemistry and its enzymatic mechanism, followed by the discussion on in vitro deacetylation assays. The biological functions of SIRT1 will be categorized into three main groups based on its substrates. Directly involved in many important cellular procedures, SIRT1 builds up the connection between epigenetics and metabolism. Since SIRT1 is important to human health, its activation and inhibition can be one of the potential treatment targets for diseases such as cancer and neurodegeneration. Our analysis is aiming to provide some new aspects into the biochemistry and chemical biology of SIRT1.